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Obesity, as a part of metabolic syndrome, represents the leading factor for disability, and is correlated with higher inflammation status, morbidity, and mortality. Biomarkers of high-level chronic inflammation are recognized as important predictors of pro-inflammatory disease. Besides the well-known pro-inflammatory cytokines, such as WBCs (white blood cells), IL-1 (interleukin-1), IL-6 (interleukin-6), TNF-alpha (tumor necrosis factor-alpha), and hsCRP (high-sensitivity C-reactive protein), as well as anti-inflammatory markers, such as adiponectin and systemic inflammation, can be determined by a variety of blood tests as a largely available and inexpensive inflammatory biomarker tool.
- morbid obesity
- pro-inflammatory status
- metabolic syndrome
- weight-loss effects
1. Introduction
According to the World Health Organization (WHO) European Regional Obesity Report in 2022, overweight and obesity have reached epidemic proportions in Europe, affecting 58% of adults and about one in three children, and the report also shows that the disease causes 200,000 cases of cancer and 1.2 million deaths per year [1]. At present, obesity is the leading factor for disability, and it has been correlated with higher morbidity and mortality since the onset of the COVID-19 pandemic [1][2].
The growing prevalence of worldwide obesity is still a major global health challenge despite all of the warning signs raised in the last two decades leading to the “most prevalent cause of human morbidity and mortality”. Obesity is a condition related to genetic, environmental, and behavioral factors, but even so, it remains a preventable and, more importantly, treatable disease. The danger of this condition comes from the fact that it leads to more serious diseases. On one hand, it is directly related to cardiovascular disease and type 2 diabetes mellitus, and on the other hand, it is involved in the appearance of certain types of cancer, but it affects almost all systems and organs of the body to varying degrees. Furthermore, musculoskeletal complications arise due to the mechanical effects of increased body weight. Excess body fat leads to premature death and is a serious risk factor for disabilities [1][3].
According to a report presented at the 2022 European Congress on Obesity, the incidence of obesity in Europe is the second highest in the world after the Americas [1]. The causes of obesity seem to be more complex than an unhealthy diet and a lack of physical activity. Mental, emotional, and physical stressors; life-specific environmental factors in modern, highly digitalized European societies, such as unhealthy food marketing online; and the preference for a sedentary lifestyle also play an important role [1][4].
The negative effects of excess fat have repercussions on all systems and organs of the body. Weight loss improves inflammation locally and systemically, given that adiposity redundancy is a form of destabilizing aggression against the immune system. A healthy and balanced lifestyle is the key to returning the body to health and equilibrium.
2. Metabolic Syndrome Exacerbates Comorbidities
The definition of metabolic syndrome (MetS) includes five criteria: (1) central obesity, defined as a large waist circumference (WC), an elevated waist–hip ratio (>0.90 for females and >0.85 for males), or a body mass index (BMI) above 30 kg/m; (2) raised blood pressure; (3) dyslipidemia, i.e., elevation of total cholesterol (TC), low-density lipoprotein (LDL), and/or triglycerides (TG), and low high-density lipoprotein cholesterol (HDL-C); (4) raised fasting plasma glucose; and (5) raised fasting serum insulin. The prevalence of MetS can increase with the prevalence of obesity as the two entities are closely related [5][6].
As previously discussed, obesity predisposes an individual to, in addition to cardiovascular disease (CD) and type 2 diabetes (T2D), a number of serious diseases, such as cholesterol gallstones, obstructive sleep apnea (OSA), non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), polycystic ovarian syndrome (PCOS), fertility disorders, gout, osteoarthritis, psoriasis, asthma, depression, and dementia. Previous studies show that various cancers, including esophageal, breast, colorectum, liver, pancreas, kidney, gallbladder, prostate/ovary, and endometrial cancer, as well as malignant melanoma, leukemia, multiple myeloma, and meningioma, seem to also be related to obesity [7].
Any three of the five abnormal findings fulfill the diagnosis of MetS. As obesity affects atherogenesis due to clinical complications, including ischemic heart disease, peripheral artery disease, cerebrovascular disease, and diabetes mellitus, some indicators for the evaluation of cardiometabolic risk have also been useful [8][9].
The accumulation of fat around the abdomen is defined as central obesity and is measured clinically with a measuring tape following the measurement of the circumference of the waist. A healthy female could have up to an 80 cm waist circumference, while a healthy man could have up to a 94 cm waist circumference. A female whose waist measures over 88 cm and a male whose waist measures over 110 cm would be diagnosed with central obesity and may present major health risks [7]. The most accepted classification of excess adiposity is the one made by the WHO, expressed as BMI, which is defined in kg (weight in kilograms)/m2 (height in square meters) [1]:
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Grade 1 obesity (commonly referred to as overweight): a BMI between 25 and 29.9 kg/m2;
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Grade 2 obesity (called obesity): a BMI between 30 and 39.9 kg/m2;
Large-scale epidemiological studies have shown that cardiovascular, metabolic, and cancer morbidity begin to increase from a BMI ≥ 25. A BMI between 25 and 30 should be considered important from a medical point of view and in terms of the need for medical care, especially in the presence of risk factors for adiposity, such as high blood pressure and glucose intolerance [1]. An increased BMI is a marker for MetS and is also used as a screening method to assess cardiometabolic risk factors (hypertension, diabetes, and cardiovascular disease), as well as a predictor of total body fat percentage and visceral fat mass [9].
3. Inflammation in Obesity: The Link Mechanism and the Complications
Increased deposits of visceral rather than subcutaneous fat, or central adiposity, is the “particular weight gain model”, while abdominal fat in particular is associated with chronic, low-grade inflammation and immune activation [10]. Visceral fat, known as “deep fat”, has a greater impact on health as it is more biologically active, has a higher density of cells, has greater blood flow, and is located closer to the portal vein, which results in an increased level of fatty acids reaching the liver [1][8].
Mammalians have three distinctive types of fat tissue: white adipose tissue (WAT), brown adipose tissue (BAT), and beige adipose tissue, with totally different biological functions. While WAT is specialized in energy storage and mobilization, hormone secretion, and immune function, BAT is specialized in energy consumption and utilizes chemical energy, which plays an essential part in the maintenance of central body temperature, i.e., thermogenesis [11][12].
An occurrence known as the “browning of WAT” was discovered through the activation or cold exposure of β-adrenergic receptors (β-ARs) shaping the so-called beige adipose tissue. By absorbing sugars and fatty acids to produce caloric heat, both brown and beige adipocytes play a major role in regulating glucose and lipid metabolism [13]. Cheng et al. confirmed the fact that the stimulation of BAT and beige AT may represent a possible strategy to treat excessive adiposity and diabetes. Research confirms that active BAT plays a major role in improving glucose and lipid metabolism. It improves glucose tolerance, insulin sensitivity, and pancreatic beta-cell function and reduces the need for insulin secretion [14].
Firstly, white fat cells widely distributed throughout the body store excess energy as triglycerides [10]. When the body needs this stored energy elsewhere, it is released as free fatty acids. Secondly, fat cells form an active metabolic organ. Adipocytes generate an impact on pancreatic beta-cell function, hepatic glucose production, muscle glucose assimilation, appetite adjustment, and arterial inflammation through various adipocytokines, such as adiponectin, leptin, resistin, and tumor necrosis factor-alpha (TNF-alpha). A process of increased lipolysis occurs at the level of visceral fat. Through this process, the flow of free acids in the liver increases, insulin resistance also increases, and there is high production of abnormal lipid particles, mainly triglycerides [9][10].
The average systolic and diastolic blood pressure increases significantly with increasing BMI. Vascular remodeling, with a significant role in arterial hypertension, occurs due to neurohormonal processes caused by excess adiposity. There is stimulation of the renin–angiotensin system (RAS), leptin activity, and the sympathetic nervous system (SNS) due to events with a pro-inflammatory role [3]. Meanwhile, cardiovascular pathologies, especially heart failure, are associated with and aggravated by obesity, with this playing a major role in the various models of remodeling of the left ventricle. Through the important chronic inflammation process, obesity contributes to the development and diversity of heart failure [15].
Second, obesity increases insulin resistance and raises circulating insulin levels, which can lead to type 2 diabetes [16]. Furthermore, obesity promotes an imbalance between glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2), impairing the incretin axis, which contributes to the appearance of insulin resistance; therefore, this whole process becomes involved in a vicious cycle [3].
In addition to all these cardiometabolic diseases, obesity through chronic inflammatory syndrome predisposes an individual to a series of overall dangerous pathophysiological changes. Insulin resistance stimulates endothelin-1 production, which further promotes increased atherogenesis and vasoconstrictor tone. Obesity is often associated with an altered lipid profile, which also contributes to the atherogenic process [3][17].
This entry is adapted from the peer-reviewed paper 10.3390/jcm12113818
References
- WHO Regional Office for Europe. Available online: https://www.who.int/europe/publications/i/item/9789289057738 (accessed on 27 June 2022).
- Vasheghani, M.; Hessami, Z.; Rekabi, M.; Abedini, A.; Qanavati, A. Evaluating Possible Mechanisms Linking Obesity to COVID-19: A Narrative Review. Obes. Surg. 2022, 32, 1689–1700.
- Triposkiadis, F.; Xanthopoulos, A.; Starling, R.C.; Iliodromitis, E. Obesity, inflammation, and heart failure: Links and misconceptions. Heart Fail. Rev. 2022, 27, 407–418.
- Wang, M.; Liu, J.; Zhang, Z.; Zhang, H.; Wang, N.; Chen, X.; Han, X.; Lu, Q.; Chi, S. Effects of Dietary Intervention on Inflammatory Markers in Metabolic Syndrome: A Systematic Review and Meta-Analysis. Front. Nutr. 2022, 9, 846591.
- Lam, D.W.; LeRoith, D. Metabolic Syndrome. In Comprehensive Free Online Endocrinology Book; NCBI: Bethesda, MD, USA, 2019; Available online: www.endotext.org (accessed on 27 June 2022).
- Nilsson, P.M.; Tuomilehto, J.; Ryden, L. The metabolic syndrome—What is it and how should it be managed? Eur. J. Prev. Cardiol. 2019, 26, 33–46.
- Barati, E.; Ghazizadeh, H.; Sadabadi, F.; Kazemi, E.; Ferns, G.A.; Avan, A.; Ghayour-Mobarhan, M. Association of the IL6 Gene Polymorphism with Component Features of Metabolic Syndrome in Obese Subjects. Biochem. Genet. 2019, 57, 695–708.
- Hamdy, O.; Uwaifo, G.I.; Oral, E.A. Obesity. Medscape, 9 June 2021.
- Gârgavu, S.R.; Clenciu, D.; Roșu, M.M.; Țenea Cojan, T.Ș.; Costache, A.; Vladu, I.M.; Moța, M. Visceral adiposity index (vai)—A potential marker of cardiometabolic risk. Arch. Balk. Med. Union 2018, 53, 246–251.
- Jameson, J.L. Harrison’s Endocrinology, 3rd ed.; McGraw Hill: New York, NY, USA, 2013.
- Eley, V.A.; Thuzar, M.; Navarro, S.; Dodd, B.R.; Zundert, A.A.V. Obesity, metabolic syndrome, and inflammation: An update for anaesthetists caring for patients with obesity. Anaesth. Crit. Care Pain Med. 2021, 40, 100947.
- Kaisanlahti, A.; Glumoff, T. Browning of white fat: Agents and implications for beige adipose tissue to type 2 diabetes. J. Physiol. Biochem. 2019, 75, 1–10.
- Lidell, M.E.; Betz, M.J.; Enerbäck, S. Brown adipose tissue and its therapeutic potential. J. Intern. Med. 2014, 276, 364–377.
- Cheng, L.; Wang, J.; Dai, H.; Duan, Y.; An, Y.; Shi, L.; Lv, Y.; Li, H.; Wang, C.; Ma, Q.; et al. Brown and beige adipose tissue: A novel therapeutic strategy for obesity and type 2 diabetes mellitus, National Library of Medicine. Adipocyte 2021, 10, 48–65.
- Mach, F.; Baigent, C.; Catapano, A.L.; Koskinas, K.C.; Casula, M.; Badimon, L.; Chapman, M.J.; De Backer, G.G.; Delgado, V.; Ference, B.A.; et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk. Eur. Heart J. 2020, 41, 111–188.
- Gallagher, E.J.; LeRoith, D.; Karnieli, E. The Metabolic Syndrome—From Insulin Resistance to Obesity and Diabetes. Med. Clin. N. Am. 2011, 95, 855–873.
- Dieny, F.F.; Tsani, A.F.A.; Suryawati, S. Visceral Adiposity Index and Lipid Accumulation Product Related to Insulin Resistance and Metabolic Syndrome in Obese College Students. Open Access Maced. J. Med. Sci. 2022, 10, 667–673.
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